Lithium antagonism of ethanol-induced intoxication: Relationship to intracellular lithium levels

Seventeen detoxified chronic alcoholics participated in a double-blind trial comparing placebo and lithium (Li⁺) effects on acute ethanol (1 g/kg) intoxication. In a repeated measures, split-half crossover design, subjects were maintained for 7 days on Li⁺ or placebo before the ethanol challenge. Plasma Li⁺ levels on day 7 averaged 1.3 ± 0.3 mM. Li⁺ was not more effective than placebo in attenuating ethanol effects across the subjective dimensions of intoxication, desire to drink, and control of drinking and across the cognitive dimensions measured by Trail Making A, Speed of Closure, and the Minnesota Clerical Test. Li⁺ was not significantly more effective than placebo in preventing the ethanol-induced rise in plasma prolactin. Subjects were divided according to high and low red blood cell (RBC) Li⁺ intracellular/extracellular Li⁺ ratios. In a comparison of the Li⁺ to placebo arms of the trial, the high ratio subjects (n=9) showed a significant 44% decrease in ethanol-induced intoxication, while the low ratio subjects (n=8) showed a 15% increase. Furthermore, the high ratio subjects performed better than the low ratio subjects, independent of the ethanol effect, on all tests of cognitive performance. These preliminary data suggest that the Li⁺ ratio may be useful tool in defining unique subgroups of alcoholic patients.